Samuel Alperin

Background: Epilepsy is a core feature of Angelman syndrome (AS) and a major contributor to morbidity and caregiver burden. The current study provides updated caregiver-reported data on seizure characteristics, triggers, and management in AS.Methods: Caregivers of 130 individuals with AS enrolled in the Linking Angelman and Dup15q Data for Expanded Research (LADDER) Database completed an online questionnaire assessing seizure characteristics, age at first seizure and diagnosis, perceived triggers, and management strategies. Participants were grouped by molecular subtype (deletion vs. non-deletion). Descriptive statistics and group comparisons were conducted.Results: Seizures were more frequently reported in individuals with deletion subtypes compared to those with non-deletion subtypes. The most common seizure-related manifestations (myoclonic, atonic, and atypical absence features) did not differ between groups. Individuals with deletion subtypes experienced earlier epilepsy diagnosis than those with non-deletion subtypes, though age at first seizure prompting medical attention did not differ significantly between the groups. About half of caregivers were unsure of seizure triggers; among identified triggers, illness or infection with a fever was most common. Pharmacological treatment was the primary management approach, with levetiracetam most frequently reported. Side effects were the most common reason for medication discontinuation, and only 69% of caregivers reported access to or use of an acute seizure rescue medication.Conclusions: Caregiver-reported data from the LADDER Database provide an updated characterization of seizures in AS. Gaps in trigger identification and availability or use of rescue medications highlight opportunities to improve standard-of-care implementation in AS.

Background: Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric difficulties, appropriately termed TSC-Associated Neuropsychiatric Disorders (TAND). The objectives of the study were to analyze the rates of TAND symptoms in a cohort of patients seen at the TSC Center of Excellence at Cincinnati Children’s Hospital and to identify clinically meaningful profiles based on TAND symptoms. Methods: Data from the TAND Checklist was obtained from participants seen at the TSC Center of Excellence at Cincinnati Children’s Hospital Medical Center from June 2015 to August 2018. Cluster and factor analyses for each TAND symptom were performed. Factor scores were then calculated for participants, and a K-means cluster analysis of these scores was used to empirically identify distinct overall TAND symptom profiles occurring in TSC. Results: A total of 1545 checklists was completed for 668 participants (37% adults and 63% children). Approximately 90% of participants reported at least one TAND symptom with an average of 12 symptoms (out of 29). Symptom rates ranged between 5 and 60%. The most common symptoms were neuropsychologic symptoms. A seven-cluster and seven-factor solution were found to be optimal. K-means cluster analysis resulted in a seven-profile solution, ranging from low to high symptom burden. Conclusion: This study is the first to identify natural phenotypic profiles of TAND symptoms. Study of specific TAND subpopulations with shared profiles may facilitate better understanding of the underlying biology of TAND and better assessment of more targeted treatments.